The silicon-oxygen (Si—O) bond is an extremely useful feature in organic chemistry, at least for its use in protecting group chemistries, its utility as a traceless directing group in organic synthesis, and its prevalence in a number of important functional material classes. The silylative protection of alcohols has further been employed in drug discovery to improve pharmacokinetic properties of pharmaceutically relevant molecules and to enhance drug toxicity.
A large number of catalytic methods for the construction of O—Si bonds have been developed (FIG. 1A). The direct silylation of alcohols by transition metal catalysis or Brønsted and Lewis acids/bases and catalytic hydrosilylation of carbonyl compounds have been the most commonly employed protocols. However, despite decades of work, the most prominent method for the construction of the Si—O bond is the treatment of alcohols with moisture-sensitive chlorosilanes in the presence of nucleophilic catalysts and a base to scavenge the HCl generated. Moreover, in certain challenging cases such as the silylene protection of 1,2-diols with certain silanes, the use of highly reactive or toxic electrophilic silicon reagents is necessary. As a result, the development of an effective, general, and convenient O—Si construction methodology which circumvents the production of stoichiometric salt by-products and avoids the use of toxic and moisture-sensitive electrophilic silicon sources, while simultaneously improving the scope in comparison to previous methods would be of considerable interest to chemists working in a variety of fields.
The present invention takes advantage of the discoveries cited herein to avoid at least some of the problems associated with previously known methods.